title: Analysis of RYR1 haplotype profile in patients with malignant hyperthermia.
abstract: This study represents a new approach to characterising patients at risk of malignant hyperthermia (MH) through the use of a recently published method for identifying high-risk haplotypes in candidate genes. We present analysis based upon the largest standardised and genotyped database of MH patients worldwide. We used unphased RYR1 SNP data directly to (1) assess RYR1 haplotype frequency differences between susceptible cases and control groups and (2) analyse population-based association via clustering of RYR1 haplotypes based on disease risk. Our results show a significant difference in RYR1 haplotype frequency between susceptible cases and UK Caucasian population controls. Furthermore we identify a high-risk cluster of haplotypes that is associated with the commonest UK MH mutation p.G2434R/c.7300G>A. These results demonstrate the applicability of this new and practical method for population based association analysis.
authors.affiliation: MH Investigation Unit, Academic Unit Anaesthesia, Leeds Institute of Molecular Medicine, St James's University Hospital, Leeds LS97TF. danielle.carpenter@nottingham.ac.uk
authors.forename: D
authors.initials: D
authors.lastname: Carpenter
authors.forename: A
authors.initials: A
authors.lastname: Morris
authors.forename: R L
authors.initials: RL
authors.lastname: Robinson
authors.forename: P
authors.initials: P
authors.lastname: Booms
authors.forename: D
authors.initials: D
authors.lastname: Iles
authors.forename: P J
authors.initials: PJ
authors.lastname: Halsall
authors.forename: D
authors.initials: D
authors.lastname: Steele
authors.forename: P M
authors.initials: PM
authors.lastname: Hopkins
authors.forename: M-A
authors.initials: MA
authors.lastname: Shaw
mesh_terms: D016022:Case-Control Studies; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D008305:Malignant Hyperthermia / Q000235:genetics*; D009154:Mutation; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D019837:Ryanodine Receptor Calcium Release Channel / Q000235:genetics*; D006113:United Kingdom; D044465:White People / Q000235:genetics
chemical_list: D019837:Ryanodine Receptor Calcium Release Channel